The results suggest that the Chinese (Cantonese) version of the Tinnitus Handicap Inventory is a reliable and valid measure of general tinnitus-related distress that can be used in clinical settings to quantify the impact of tinnitus on daily life.
Diffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury.
ObjectivesThe role of microRNAs in association with Mycobacterium tuberculosis (MTB) infection and the immunology regulated by microRNAs upon MTB infection have not been fully unravelled. We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of Beijing/W and non-Beijing/W clinical strains. We also studied the microRNA profiles of the host macrophages by microarray in a small cohort with active MTB disease, latent infection (LTBI), and from healthy controls.ResultsThe results revealed that 14 microRNAs differentiated infections of Beijing/W from non-Beijing/W strains (P<0.05). A unique signature of 11 microRNAs in human macrophages was identified to differentiate active MTB disease from LTBI and healthy controls. Pathway analyses of these differentially expressed miRNAs suggest that the immune-regulatory interactions involving TGF-β signalling pathway take part in the dysregulation of critical TB processes in the macrophages, resulting in active expression of both cell communication and signalling transduction systems.ConclusionWe showed for the first time that the Beijing/W TB strains repressed a number of miRNAs expressions which may reflect their virulence characteristics in altering the host response. The unique signatures of 11 microRNAs may deserve further evaluation as candidates for biomarkers in the diagnosis of MTB and Beijing/W infections.
Tuberculosis remains an important disease worldwide. The emergence of multidrug resistance in strains of Mycobacterium tuberculosis (M. tuberculosis) is one of the most important threats to tuberculous control. Despite continued efforts directed to improve tuberculosis control programs at national and international levels, recent surveys reveal that drug-resistant tuberculosis is still ubiquitous and rates of infection are alarmingly high in several countries. According to Espinal et al. (9), multidrug-resistant tuberculosis (MDR-TB) defining as resistance to at least isoniazid (INH) and rifampin (RIF) was present among new cases in 54 of 58 surveyed geographic sites in 1996 to 1999. Among new cases, alarming rates were reported in Estonia (14.1%), Latvia (9.0%), Tomsk Oblast of Russian Federation (6.5%), Ivanovo Oblast of the Russian Federation (9.0%), and Henan of China (10.8%). Overall, in all 58 surveyed sites and among the previously treated cases (9), the median MDR-TB rate was 9.3%, and for 35 geographic sites it was present at rates of 5% or higher.In M. tuberculosis, monoresistance to RIF is rare, and at least 90% of all RIF-resistant clinical isolates are also resistant to isoniazid (7). Hence, a positive result for RIF resistance would be useful as a strong surrogate of MDR-TB. In resistant isolates, it has been shown that up to 95 to 98% RIF resistance is caused by mutations in the rpoB gene encoding the RNA polymerase -subunit. In the great majority of the RIF-resistant isolates, mutations occurred within a 81-bp hotspot region (the rifampin resistance determining region [RRDR], encoding 27 amino acids and corresponding to codons 507 to 533 or cluster I according to Escherichia coli numbering) in the center of the 3,516-bp rpoB gene (24). Within the RRDR, more than 80 distinct variants of single-base mutations or in-frame deletions or insertions have been reported among RIF-resistant isolates. Although several different molecular techniques such as heteroduplex analysis, line probe assay, and PCR singlestrand conformational length polymorphism have been used for analysis of rpoB gene mutations, these techniques were limited in that only the most frequent types of mutations were included.In the present study we report a rapid assay based on PCR and sequencing of the rpoB gene for direct detection of RRDR-associated RIF-resistant M. tuberculosis in clinical isolates and respiratory specimens. A total of 2,138 respiratory specimens and 142 M. tuberculosis isolates were used to evaluate the specificity and sensitivity of this assay. The results were compared to commercial and in-house diagnostic assays for M. tuberculosis and phenotypic drug susceptibility testing. MATERIALS AND METHODS Specimens and isolates.Between March 1999 and October 2002, 2,138 respiratory specimens (1,807 expectorated sputum and 331 bronchoalveolar lavage samples) were collected from 1571 patients suffering from chest symptoms and/or chest radiographic infiltrates of undetermined origin, including 712 pa-
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